West Nile virus infection has become an emerging infectious disease in the United States. The virus infects birds, the natural reservoir of the virus, and is transmitted to humans by the bite of the Culex mosquito. The virus has been found in bird populations in most of the eastern and Midwestern parts of the US, and is projected to reach the west coast in 2-3 years. While infected humans may be asymptomatic or have flu-like symptoms, some (<1%) progress to develop severe neurological symptoms. Approximately 5-14% of the latter cases are fatal, and a high percentage of the non-fatal cases result in permanent neurological disabilities. Moreover, the fatality case rate is more than twice as high in victims over the age of 70 than in the general population. Currently, there is no approved commercially available vaccine for West Nile virus infection, nor is there any specific therapy for disease, only symptomatic treatment. The long-term goal of this research is to produce a safe and effective vaccine for West Nile virus infection in humans. The specific aim of this proposal is to test the efficacy of a candidate vaccine developed at Hawaii Biotech in an established animal model of West Nile virus infection. The candidate vaccine is a recombinant subunit vaccine in which the immunogens are a modified envelope protein plus a non-structural protein from the West Nile virus. The recombinant proteins are produced by a proprietary method of expression and purified by immunoaffinity chromatography. The vaccine will be tested for immunogenicity in mice and for protective efficacy in the golden hamster model of West Nile virus encephalitis. [unreadable] [unreadable] [unreadable]